12-107000270-C-T

Variant names:

• chr12-107000270-C-T
• rs10861688
• NM_004075.5:c.685-188G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004075.5(CRY1):​c.685-188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,978 control chromosomes in the GnomAD database, including 1,990 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1990 hom., cov: 32)
• Consequence: CRY1 NM_004075.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 17 publications found

Genes affected

CRY1 (HGNC:2384): (cryptochrome circadian regulator 1) This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been associated with altered sleep patterns. The encoded protein is widely conserved across plants and animals. Loss of the related gene in mouse results in a shortened circadian cycle in complete darkness. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004075.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	NM_004075.5	MANE Select	c.685-188G>A		intron	N/A	NP_004066.1
	CRY1	NM_001413458.1		c.685-188G>A		intron	N/A	NP_001400387.1
	CRY1	NM_001413459.1		c.685-188G>A		intron	N/A	NP_001400388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRY1	ENST00000008527.10	TSL:1 MANE Select	c.685-188G>A		intron	N/A	ENSP00000008527.5
	CRY1	ENST00000546722.1	TSL:3	n.178-188G>A		intron	N/A
	CRY1	ENST00000552790.5	TSL:2	n.1244-188G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22449 AN: 151864 Hom.: 1989 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22455 AN: 151978 Hom.: 1990 Cov.: 32 AF XY: 0.148 AC XY: 11016 AN XY: 74284

African (AFR) AF: 0.0582 AC: 2416 AN: 41486

American (AMR) AF: 0.142 AC: 2163 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5164

South Asian (SAS) AF: 0.184 AC: 886 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1674 AN: 10498

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12984 AN: 67952

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.175 Hom.: 8315

Bravo AF: 0.143

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10861688; hg19: chr12-107394048;